Fallopian Tube Cancer, Ovarian Cancer, Primary Peritoneal Cancer
Conditions
Keywords
recurrent ovarian cancer, platinum-refractory ovarian cancer
Brief summary
This is a study to find out if the study drug, panitumumab, when given with gemcitabine works in treating ovarian cancer and to find out what side effects occur when they are given together.
Detailed description
Epithelial ovarian cancer (EOC) remains a leading cause of gynecologic cancer mortality in women, with more than 22,000 deaths per year in the United States alone. Due to the lack of effective screening strategies and subtle early symptoms, eighty percent of newly diagnosed patients have disease that is advanced. Despite cytoreductive surgery and adjuvant paclitaxel-based and platinum-based chemotherapy, 5-year survival rates continue to be less than 40%. For patients who become resistant to the platinum compounds (defined as progressive disease while on a platinum-based chemotherapy regimen (refractory) or within 6 months of completing a platinum-based chemotherapy regimen (resistant)),the outlook is particularly poor, and often heralds multi-drug resistant disease. At the present time, the management of ovarian cancer in the platinum refractory disease state is limited to palliative intent. Patients with advanced, bulky tumors, poor performance status and nutritional compromise are unlikely to respond to therapy and may be best served by supportive care. The clinical management of refractory disease requires both patience and persistence. A patient with platinum refractory disease is begun on one of the agents with activity and an evaluation of response is made every 6-8 weeks of therapy. As long as the patient shows no signs of disease progression, the therapy can be continued unless there is unacceptable toxicity. When progressive disease is observed, another of the list of available agents can be used. It is likely that patients will receive multiple single agents during the chronic phase of their illness. Every effort should be made to balance disease response with toxicity and quality of life. Based on this rational, this trial will be conducted to evaluate the safety and efficacy of panitumumab, a human antibody targeted to the EGF-R, and Gemcitabine, in treating women with recurrent platinum-refractory/resistant EOC. Our aim is to determine the safety and feasibility of gemcitabine and panitumumab therapy in this population and once completed, to proceed with an efficacy study using an expanded cohort.
Interventions
BIOLOGICALPanitumumab
Panitumumab 2.5 mg/kg on D1, D8, D15, and D22 and Gemcitabine 800 mg/m2 on D1, D8, and D15 of each 28 day cycle.
Sponsors
Amgen
Women and Infants Hospital of Rhode Island
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed diagnosis of metastatic, advanced, or recurrent platinum-resistant epithelial ovarian, primary peritoneal or fallopian tube cancer. * Prior first line therapy with a platinum and taxane based combination as adjuvant therapy * Measurable disease defined by RECIST criteria * Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care. * Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study. * age \> 18 * Karnofsky performance status \> 70 * Up to three prior lines of cytotoxic therapy in the setting of recurrent disease. * Estimated life expectancy of at least 3 months * Women of child-bearing potential must have a negative pregnancy test * Adequate hematopoietic function defined as: * ANC ≥ 1500/mm3 * Platelets ≥ 100,000/mm3 * Hemoglobin ≥ 9 g/dL * Magnesium ≥ lower limit of normal * Calcium ≥ lower limit of normal * Adequate renal and hepatic function defined as: * Bilirubin ≤ 1.5 times upper limit of normal (ULN) * SGOT ≤ 3 times ULN * Alanine aminotransferase (ALT) ≤3xULN (if liver metastases ≤5xULN) * Alkaline phosphatase ≤ 3 times ULN * Creatinine ≤ 1.5 mg/dL times ULN * Creatinine clearance ≤ 50 mL/min
Exclusion criteria
* Prior anti-EGFr antibody therapy (e.g., cetuximab) or treatment with small molecule EGFr inhibitors (e.g., gefitinib, erlotinib, lapatinib) * Prior treatment with gemcitabine * Radiotherapy ≤ 14 days prior to enrollment. * More than three lines of systemic chemotherapy for recurrent or advanced disease. Prior hormonal therapy is allowed. * Prior immunotherapy, or experimental or approved proteins/antibodies * Female subject is pregnant or breast-feeding. * Patient has received other investigational drugs within 28 days before enrollment * Serious medical or psychiatric illness likely to interfere with participation in this clinical study. * Prior treatment with panitumumab * Concurrent uncontrolled illness * Ongoing or active infection * History or active secondary cancer within the last 5 years, except for superficial basal cell skin cancers, curatively resected non-melanoma skin cancer * Psychiatric illness or social situation that would preclude study compliance. * History or known presence of central nervous system (CNS) metastasis * Subjects requiring chronic use of immunosuppressive agents (e.g., methotrexate, cyclosporine) * Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) \< 1 year before randomization * History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or any evidence of interstitial lung disease on baseline chest CT scan * Known positive test(s) for human immunodeficiency virus infection, hepatitis C virus, acute or chronic active hepatitis B infection * Major surgery within 28 days or minor surgery within 14 days of study enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate, Measured by RECIST Criteria | Every 8 weeks while on-study | Documentation of known measurable or evaluable disease parameters after every 2 cycles of treatment. If any patient is withdrawn for the study prior to completion of therapy a repeat evaluation will be done at that time. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events, Measured by Active Version of the NCI Common Toxicity Criteria | Every 4 weeks while on-study, up to 24 weeks | Adverse events (AEs) will be recorded during the duration of the trial, whether or not the events are considered related to medication. All AEs considered to be related to trial therapy will be followed for resolution, including into the post-treatment period. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Panitumuab and Gemcitabine Panitumumab: Panitumumab 2.5 mg/kg on D1, D8, D15, and D22 and Gemcitabine 800 mg/m2 on D1, D8, and D15 of each 28 day cycle. | 8 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Panitumuab and Gemcitabine |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants |
| Region of Enrollment United States | 8 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 8 / 8 |
| serious Total, serious adverse events | 3 / 8 |
Outcome results
Primary
Overall Response Rate, Measured by RECIST Criteria
Documentation of known measurable or evaluable disease parameters after every 2 cycles of treatment. If any patient is withdrawn for the study prior to completion of therapy a repeat evaluation will be done at that time.
Time frame: Every 8 weeks while on-study
Population: Due to the small number of participants, data were not collected as planned
Secondary
Adverse Events, Measured by Active Version of the NCI Common Toxicity Criteria
Adverse events (AEs) will be recorded during the duration of the trial, whether or not the events are considered related to medication. All AEs considered to be related to trial therapy will be followed for resolution, including into the post-treatment period.
Time frame: Every 4 weeks while on-study, up to 24 weeks
Population: Please see results section. In short, there were 3 serious adverse events (1 thromboembolic, 1 hypomagnesemia, 1 bowel obstruction). Additional adverse events included (in decreasing order) rash, fatigue, anemia, edema, thrombocytopenia, abdominal pain, epistaxis, hypocalcemia, and calciphylaxis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Panitumuab and Gemcitabine | Adverse Events, Measured by Active Version of the NCI Common Toxicity Criteria | 8 participants |